Recent work has shown that packaging of the cellular protein cyclophilin A plays an important role in HIV-1 replication. Cyclophilin A incorporates into HIV-1 virions by virtue of binding to CA. To understand this interaction, the investigator will determine the crystal structure of cyclophilin A bound to a truncated form of CA. The truncated form binds cyclophilin A with the same affinity as full-length CA, but is a monomer rather than a dimer. Preliminary results show co-crystals that diffract to 2.5 A. In addition, binding of cyclophilin to a capsid peptide will be characterized biochemically and structurally. In particular the conformation of Pro90 in CA bound to cyclophilin A suggests that this residue may act as a substrate for cyclophilin rotamase activity. Finally, genetic analysis of mutants of CA in an HIV provirus will be used to test models that arise from the CA and CA-cyclophilin structures.